In recent decades, scientists have made great strides in understanding psychiatric disorders.
They’ve identified various genetic mutations and protein dysregulations that could be behind conditions like autism spectrum disorder (ASD), schizophrenia, and Alzheimer’s disease.
Despite these advancements, some proteins’ roles in the brain are still not fully understood. One such protein is indoleamine 2,3-dioxygenase 2 (IDO2), an enzyme found in the brain and processed through the tryptophan–kynurenine pathway (TKP).
The TKP and its metabolites have been linked to several psychiatric disorders. Researchers use genetically modified mice to study these links, but IDO2’s specific functions in the brain remained unclear.
To address this, Associate Professor Yasuko Yamamoto and her team from Fujita Health University, Japan, delved into the impact of IDO2 on behavioral patterns in mice. Their findings were published in The FEBS Journal.
The researchers compared the behavior of normal mice with genetically modified mice lacking the IDO2 gene, known as IDO2 knock-out (KO) mice. These KO mice displayed several behavioral abnormalities typical of ASD.
They struggled to adapt to new environments, showed repetitive grooming, and had limited interest in their surroundings. Social interaction tests also revealed that these mice had difficulty learning from others.
The team then investigated the biochemical effects of the absence of IDO2. They found that removing IDO2 altered levels of tryptophan metabolites and affected the TKP.
Particularly noteworthy were the changes in dopamine release and uptake in the brain’s striatum and amygdala regions.
This imbalance led to a reduction in molecules involved in the dopamine D1 receptor signaling pathway, including brain-derived neurotrophic factor (BDNF), which is crucial for neuron formation and brain adaptability (neuroplasticity).
Morphological analysis of neurons in the striatum showed that IDO2 KO mice had a higher density of immature dendritic spines. Additionally, changes were observed in microglia cells, which are vital for pruning excess synapses during brain development.
In IDO2 KO mice, these cells shifted from a ‘surveillant’ type, which oversees synaptic removal, to an ‘ameboid’ type. This shift, along with BDNF dysregulation, could be responsible for the ASD-like behaviors observed.
Interestingly, chemically restoring IDO2 production in genetically modified mice resulted in behaviors similar to normal mice.
Furthermore, genetic analysis of 309 clinical brain samples from ASD patients identified a 16-year-old girl with an IDO2 gene mutation, suggesting a possible link to her symptoms.
This research could be a significant step towards understanding the genetic and biochemical aspects of psychiatric and neurodevelopmental disorders.
While more research is needed to clarify the mechanisms involved, Assoc. Prof. Yamamoto’s work provides valuable insights into the pathophysiology associated with IDO2.
If you care about autism, please read studies that cats may help decrease anxiety for kids with autism and new study may develop better treatment for autism
For more information about health, please see recent studies about how to eat your way to a healthy brain, and results showing this type of food may contribute to autism.
The research findings can be found in The FEBS Journal.
Copyright © 2023 Knowridge Science Report. All rights reserved.
